Enterovirus 71 infection of human airway organoids reveals VP1-145 as a viral infectivity determinant.

Enterovirus 71 infection of human airway organoids reveals VP1-145 as a viral infectivity determinant.
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DOI:
10.1038/s41426-018-0077-2
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发表时间:
2018-05-09
影响因子:
13.2
通讯作者:
Wolthers KC
Wolthers KC
中科院分区:
医学2区
文献类型:
--
作者:
van der Sanden SMG;Sachs N;Koekkoek SM;Koen G;Pajkrt D;Clevers H;Wolthers KC

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人类肠道病毒经常引起儿童严重疾病。人类肠道病毒通过粪口途径和呼吸道飞沫传播,主要复制发生在胃肠道和呼吸道;然而,肠道病毒如何感染这些部位在很大程度上是未知的。人类肠道类器官最近被证明是研究肠道中肠道病毒-宿主相互作用的有价值的工具。在这项研究中,我们证明了一个新开发的人类气道类器官模型肠道病毒71(EV 71)感染的易感性。我们首次在人类生理模型中显示EV 71复制动力学是菌株依赖性的。在VP 1衣壳蛋白的位置145处的谷氨酰胺被鉴定为感染性的关键决定因素,并且残基VP 1 - 98 K和VP 1 - 104 D被鉴定为潜在的感染性标记。这项研究的结果为EV 71在人类气道上皮中的感染性提供了新的见解,并证明了类器官技术对病毒研究的价值。
Human enteroviruses frequently cause severe diseases in children. Human enteroviruses are transmitted via the fecal–oral route and respiratory droplets, and primary replication occurs in the gastro-intestinal and respiratory tracts; however, how enteroviruses infect these sites is largely unknown. Human intestinal organoids have recently proven to be valuable tools for studying enterovirus–host interactions in the intestinal tract. In this study, we demonstrated the susceptibility of a newly developed human airway organoid model for enterovirus 71 (EV71) infection. We showed for the first time in a human physiological model that EV71 replication kinetics are strain-dependent. A glutamine at position 145 of the VP1 capsid protein was identified as a key determinant of infectivity, and residues VP1-98K and VP1-104D were identified as potential infectivity markers. The results from this study provide new insights into EV71 infectivity in the human airway epithelia and demonstrate the value of organoid technology for virus research.
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